Widespread elimination of naturally occurring neuronal death in Bax-deficient mice.
The proapoptotic molecule BAX is required for death of sympathetic and motor neurons in the setting of trophic factor deprivation. Furthermore, adult Bax-/- mice have more motor neurons than do their wild-type counterparts. These findings raise the possibility that BAX regulates naturally occurring cell death during development in many neuronal populations. To test this idea, we assessed apoptosis using TUNEL labeling in several well-studied neural systems during embryonic and early postnatal development in Bax-/- mice. Remarkably, naturally occurring cell death is virtually eliminated between embryonic day 11.5 (E11.5) and postnatal day 1 (PN1) in most peripheral ganglia, in motor pools in the spinal cord, and in the trigeminal brainstem nuclear complex. Additionally, reduction, although not elimination, of cell death was noted throughout the developing cerebellum, in some layers of the retina, and in the hippocampus. Saving of cells was verified by axon counts of dorsal and ventral roots, as well as facial and optic nerves that revealed 24-35% increases in axon number. Interestingly, many of the supernumerary axons had very small cross-sectional areas, suggesting that the associated neurons are not normal. We conclude that BAX is a critical mediator of naturally occurring death of peripheral and CNS neurons during embryonic life. However, rescue from naturally occurring cell death does not imply that the neurons will develop normal functional capabilities.
White
F A
FA
Department of Neurology, Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Keller-Peck
C R
CR
Knudson
C M
CM
Korsmeyer
S J
SJ
Snider
W D
WD
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D017209:Apoptosis / Q000502:physiology; D001284:Atrophy; D001921:Brain / Q000196:embryology / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003391:Cranial Nerves / Q000196:embryology / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000502:physiology; D005724:Ganglia / Q000196:embryology / Q000502:physiology; D005727:Ganglia, Spinal / Q000196:embryology / Q000502:physiology; D051379:Mice / Q000196:embryology; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000172:deficiency*; D019253:Proto-Oncogene Proteins c-bcl-2; D013116:Spinal Cord / Q000196:embryology / Q000502:physiology; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein